PROPOSAL (Adapted from the applicant's abstract): The long-term goal of the principal investigator (PI) is to become a clinician scientist examining issues pertaining to autonomic regulation in health and disease. The main objective of this project is to examine the metabolic and mechanical factors that initiate and sustain the muscle exercise pressor reflex. This reflex is a major determinant of blood flow and pressure during exercise. In addition, diseases, such as congestive heart failure (CHF) are associated with pathologic activation of this reflex and may contribute to the morbidity and mortality of this common disorder. Two basic theoretical components of neural control of circulation predominate. "Central command," a feed forward signal emanating from the central motor areas, suggests that neural motor and sympathetic activation occur in parallel. This system may be integrally linked to skeletal muscle metabolic demand. The second component of the reflex is the muscle reflex, and is the subject of this investigation. It is clear chemical byproducts of muscle contraction can evoke a pressor response. However, the specific interstitial chemical(s) that stimulate the muscle fiber afferents, and engage the reflex, remains an area of considerable controversy. This study proposes investigation of the relationship between interstitial potassium concentration and muscle sympathetic nervous activity (MSNA). Recent studies have implicated potassium as a potential mediator of the muscle reflex; however, conclusive evidence linking interstitial K+ with MSNA does not exist. The investigators will examine the "real time" interstitial concentration of potassium in exercising muscle and MSNA simultaneously, as well as venous plasma effluent, to further our understanding of this relationship. In addition, they propose examination of the exercise pressor response after directly inhibiting Na+/K+ pump with regional digoxin administration. This project will further increase their knowledge of the mechanisms regulating the muscle exercise pressor response, and may add to understanding of the role of this reflex in diseases such as CHF. The PI has been funded by an NRSA (F32 HL10320). This proposal will give the PI the additional support and training necessary to become an independent investigator. The mentor for this project has recently received a K24 Award and is the Program Director (PD) of their General Clinical Research Center (GCRC). Accordingly, he is ideally suited to serve in this capacity.